In the coming year we plan to continue to use the techniques of theoretical chemistry to identify and calculate fundamental molecular properties that explain observed agonist/antagonist activity profiles in diverse classes of opiate narcotics. In particular, conformational and electronic properties will be calculated for selected peptide opiates and unusual benzomorphan analogs. The results will be used to verify and refine hypothesized requirements for agonist/antagonist activity developed in our current studies of other classes of opiates and their interaction with model receptor sites. If our efforts are successful, the results will provide new insights into how diverse classes of opiates bind and act at similar receptor sites and how this interaction leads to agonist and antagonist activity. Furthermore, new analogs with mixed agonist/antagonist activity, and hence with potentially low physical-dependence liability, will be suggested for synthesis, receptor binding assays, and animal testing.